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Hormonal Responses to Fenfluramine in Depressive Subtypes

  • Philip Mitchell (a1), George Smythe (a2), Gordon Parker (a3), Kay Wilhelm (a4), Ian Hickie (a4), Henry Brodaty (a5) and Philip Boyce (a3)...

In order to study putative differences in central neurotransmitter function in depressive subtypes, serum Cortisol and prolactin responses to the putative serotonin agonist fenfluramine were examined in 30 subjects with major depression. Patients with endogenous depression (melancholia) as defined by each of ICD–9, DSM–III, RDC and Newcastle scale demonstrated a reduced prolactin response to 60 mg oral fenfluramine when compared with non-endogenous subjects. This was independent of either prolactin or Cortisol baseline levels, and indicates that there are differences in brain neurotransmitter function in the endogenous and non-endogenous subtypes of depression. Basal prolactin levels were reduced in bipolar compared with unipolar subjects, and delusional compared with non-delusional patients, although there were no differences in the prolactin responses to fenfluramine between these subgroups. Basal Cortisol levels and Cortisol response to fenfluramine did not distinguish between any of the subtypes.

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Corresponding author
Mood Disorders Unit, Prince Henry Hospital, Little Bay, NSW, 2036 Australia
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American Psychiatric Association (1980) Diagnostic and Statistical Manual of Mental Disorders (3rd edn) (DSM–III). Washington, DC: APA.
Anderson, I. M., Crook, W. S., Garside, S. E., et al (1989) Effect of moderate weight loss on prolactin secretion in normal female volunteers. Psychiatry Research, 29, 161167.
Andreasen, N. C. (1982) Concepts, diagnosis and classification. In Handbook of Affective Disorders (ed. E. S. Paykel), pp. 2444. Edinburgh: Churchill Livingstone.
Barbieri, C., Bigatti, G., Rauhe, W. G., et al (1984) Serotonergic regulation of Cortisol secretion in dogs. Endocrinology, 115, 748751.
Baumgartner, A., Graef, K-J. & Kuerten, I. (1988) Prolactin in patients with major depressive disorders and in healthy subjects: 1. Cross-sectional study of basal and post-TRH and post-dexamethasone prolactin levels. Biological Psychiatry, 24, 249267.
Brodaty, H., Boyce, P., Wilhelm, K., et al (1987) The establishment of a mood disorders unit. Australian and New Zealand Journal of Psychiatry, 21, 375382.
Carney, M. W. P., Roth, M. & Garside, R. F. (1965) The diagnosis of depressive symptoms and the prediction of ECT response. British Journal of Psychiatry, 111, 639645.
Carroll, B. J. (1989) Diagnostic validity of laboratory studies: rules of the game. In The Validity of Psychiatric Diagnosis (eds L. Robins & J. E. Barrett). New York: Raven Press.
Carroll, B. J., Feinberg, M., Greden, J. F., et al (1980) Diagnosis of endogenous depression: comparison of clinical research and neuroendocrine criteria. Journal of Affective Disorders, 2, 177194.
Carroll, B. J., Feinberg, M., Greden, J. F., et al (1981) A specific laboratory test for the diagnosis of melancholia. Standardization, validation and clinical utility. Archives of General Psychiatry, 38, 1522.
Checkley, S. A. (1979) Corticosteroid and growth hormone responses to methylamphetamine in depressive illness. Psychological Medicine, 9, 107115.
Checkley, S. A. (1980) Neuroendocrine tests for monoamine function in man: a review of basic theory and its application to the study of depressive illness. Psychological Medicine, 10, 3553.
Checkley, S. A., Glass, I. B., Thompson, C., et al (1984) The GH response to clonidine in endogenous as compared with reactive depression. Psychological Medicine, 14, 773777.
Coccaro, E. F., Siever, L. J., Klar, H. M., et al (1989) Serotonergic studies in patients with affective and personality disorders: correlations with suicidal and impulsive aggressive behaviour. Archives of General Psychiatry, 46, 587599.
Cowen, P. J. & Charig, E. M. (1987) Neuroendrocrine responses to intravenous tryptophan in major depression. Archives of General Psychiatry, 44, 958966.
Davidson, J., Turnbull, C., Strickland, R., et al (1984) Comparative diagnostic criteria for melancholia and endogenous depression. Archives of General Psychiatry, 41, 506511.
Dolan, R. H. & Calloway, S. P. (1986) The human growth hormone response to clonidine: relationship to clinical and neuroendocrine profile in depression. American Journal of Psychiatry, 143, 772774.
Farmer, A. & McGuffin, P. (1989) The classification of the depressions: contemporary confusion revisited. British Journal of Psychiatry, 155, 437443.
Foulds, G. A. (1973) The relationship between the depressive illnesses. British Journal of Psychiatry, 123, 531533.
Gillespie, R. D. (1929) The clinical differentiation of types of depression. Guy's Hospital Reports, 79, 306344.
Hamilton, M. (1967) Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology, 6, 278296.
Heninger, G. R., Charney, D. S. & Sternberg, D. E. (1984) Serotonergic function in depression: prolactin response to intravenous tryptophan in depressed patients and healthy subjects. Archives of General Psychiatry, 41, 398402.
Horton, R. W., Katona, C. L. E., Theodorou, A. E., et al (1986) Platelet radioligand binding and neuroendocrine challenge tests in depression. In Antidepressants and Receptor Function, Ciba Foundation Symposium, No. 123, pp. 84105. Chichester: Wiley.
Hsiao, J. K., Bartko, J. J. & Potter, W. Z. (1989) Diagnosing diagnoses: receiver operating characteristic methods and psychiatry. Archives of General Psychiatry, 46, 664667.
Jackson, R. V., Grice, J. E. & Jackson, A. J. (1988) Inhibition of serotonin-induced ACTH release in man by clonidine. Clinical and Experimental Pharmacology and Physiology, 15, 293298.
Joyce, P. R., Sellman, J. D., Donald, R. A., et al (1988) The unipolar-bipolar depressive dichotomy and the relationship between afternoon prolactin and Cortisol levels. Journal of Affective Disorders, 14, 189193.
Joyce, P. R. & Paykel, E. S. (1989) Predictors of drug response in depression. Archives of General Psychiatry, 46, 8999.
Lewis, D. A. & Sherman, B. M. (1984) Serotonergic stimulation of adrenocorticotropin secretion in man. Journal of Clinical Endocrinology and Metabolism, 58, 458462.
Lopez-Ibor, J. J., Saiz-Ruiz, J. & Iglesias, L. M. (1988) The fenfluramine challenge test in the affective spectrum: a possible marker of endogeneity and severity. Pharmacopsychiatry, 21, 914.
Lopez-Ibor, J. J., Saiz-Ruiz, J. & Iglesias, L. M. (1989) Neuroendocrine challenges in the diagnosis of depressive disorders. British Journal of Psychiatry, 154 (suppl. 4), 7376.
Lykouras, E., Markianos, M., Milliaras, D., et al (1988) Neurochemical variables in delusional depression. American Journal of Psychiatry, 145, 214217.
Madansky, A. (1988) Prescriptions for Working Statisticians. New York: Springer-Verlag.
Maes, M., De Ruyter, M., Claes, R., et al (1987) The Cortisol responses to 5-hydroxytryptophan, orally, in depressive inpatients. Journal of Affective Disorders, 13, 2330.
Matussek, N., Ackenheil, M., Hippius, H., et al (1980) Effect of clonidine on growth hormone release in psychiatric patients and controls. Psychiatry Research, 2, 2536.
Meltzer, H. Y., Umberkoman-Wiita, B., Robertson, A., et al (1984) Effect of 5-hydroxytryptophan on serum Cortisol levels in major affective disorders: 1. Enhanced response in depression and mania. Archives of General Psychiatry, 41, 366374.
Mendlewicz, J., Van Cauter, E., Linkowski, , et al (1980) The 24–hour profile of prolactin in depression. Life Sciences, 27, 20152024.
Mitchell, P. & Smythe, G. (1990) Hormonal responses to fenfluramine in depressed and control subjects. Journal of Affective Disorders, 19, 4356.
Nutt, D. J. & Cowen, P. J. (1987) Diazepam alters brain 5-HT function in man: implications for the acute and chronic effects of benzodiazepines. Psychological Medicine, 17, 601607.
Quattrone, A., Tedeschi, G., Aguglia, U., et al (1983) Prolactin secretion in man: a useful tool to evaluate the activity of drugs on central 5-hydroxytryptaminergic neurones. Studies with fenfluramine. British Journal of Clinical Pharmacology, 16, 471475.
Roy, A., Pickar, D., Linnoila, M., et al (1985) Plasma norepinephrine level in affective disorders. Archives of General Psychiatry, 42, 11811185.
Roy, A., Pickar, D., Douillet, P., et al (1986) Urinary monoamines and monoamine metabolites in subtypes of unipolar depressive disorder and normal controls. Psychological Medicine, 16, 541546.
Shapira, B., Reiss, A., Kaiser, N., et al (1989) Effect of imipramine treatment on the prolactin response to fenfluramine and placebo challenge in depressed patients. Journal of Affective Disorders, 16, 14.
Siever, L. J., Murphy, D. L., Slater, S., et al (1984) Plasma prolactin changes following fenfluramine in depressed patients compared to controls: an evaluation of central serotonergic responsivity in depression. Life Sciences, 34, 10291039.
Smythe, G. A., Bradshaw, J. E., Cai, W. Y., et al (1982) Hypothalamic serotonergic stimulation of thyrotropin secretion and related brain-hormone and drug interactions in the rat. Endocrinology, 111, 11811191.
Spitzer, R. L., Endicott, J. & Robins, E. (1978) Research diagnostic criteria: rationale and reliability. Archives of General Psychiatry, 35, 773782.
Storlien, L. H. & Smythe, G. A. (1990) D-fenfluramine effects on hypothalamic monoamine activities and their hormonal correlates. Life Sciences (in press).
Van de Kar, L. D., Urban, J. H., Richardson, K. D., et al (1985) Pharmacological studies on the serotonergic and non-serotonin-mediated stimulation of prolactin and corticosterone secretion by fenfluramine. Neuroendocrinology, 41, 283288.
Van Praag, H. M., Korf, J. & Puite, J. (1970) 5-hydroxyindo-leacetic acid levels in the cerebrospinal fluid of depressive patients treated with probenecid. Nature, 225, 12591260.
Van Praag, H. M., Lemus, C. & Kahn, R. (1987) Hormonal probes of central serotonergic activity: do they really exist? Biological Psychiatry, 22, 8698.
Weizman, A., Mark, M., Gil-Ad, I., et al (1988) Plasma Cortisol, prolactin, growth hormone and immunoreactive B-endorphin response to fenfluramine challenge in depressed patients. Clinical Neuropharmacology, 11, 250256.
Willoughby, J., Menadue, M. & Jervois, P. (1982) Function of serotonin in physiological secretion of growth hormone and prolactin and p-clorophenylalanine. Brain Research, 249, 291299.
World Health Organization (1978) Mental Disorders: Glossary and Guide to their Classification in Accordance with the Ninth Revision of the International Classification of Disease (ICD–9). Geneva: WHO.
Zung, W. W. K. (1965) A self-rated depression scale. Archives of General Psychiatry, 12, 6370.
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Hormonal Responses to Fenfluramine in Depressive Subtypes

  • Philip Mitchell (a1), George Smythe (a2), Gordon Parker (a3), Kay Wilhelm (a4), Ian Hickie (a4), Henry Brodaty (a5) and Philip Boyce (a3)...
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